Inhibition of angiogenesis by rhizoxin, a microbial metabolite containing two epoxide groups.
Previous studies by our and other groups have shown that microbial products containing more than one epoxide group, including eponemycin, radicicol, depudecin and AGM-1470, exhibits anti-angio-genic activity in an in vivo assay system involving chorioallantoic membranes (CAMs) of growing chick embryos. Based on these findings, rhizoxin, a microbial metabolite that contains two epoxide groups and exhibits anti-tubulin activity, was tested for anti-angiogenic activity in a CAM assay system. Rhizoxin caused dose-dependent inhibition of embryonic angiogenesis, the ID50 value being 2 ng (3.2 pmol) per egg. In addition, this compound (2 mg/kg i.p.) significantly suppressed neovascularization induced by M5076 mouse tumor cells in a mouse dorsal air sac assay system, compared to the vehicle alone (P < 0.05). These results indicate that rhizoxin is a novel inhibitor of angiogenesis, and that is has potential as a new therapeutic agent for cancer.
Onozawa
C
C
Department of Cancer Therapeutics, Tokyo Metropolitan Institute of Medical Science (Rinshoken).
Shimamura
M
M
Iwasaki
S
S
Oikawa
T
T
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004852:Epoxy Compounds / Q000737:chemistry; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D018942:Macrolides; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D013125:Spinal Neoplasms / Q000098:blood supply; D013126:Spinal Nerve Roots / Q000098:blood supply
D000903:Antibiotics, Antineoplastic; D004852:Epoxy Compounds; D007783:Lactones; D018942:Macrolides; C041443:rhizoxin